Scientists

Question 1

Paul Ehrlich

Answer 1

“compara nongunt nisi fixata”
-agents only work when they are bound
-binding interactions are critical for a drugs MOA and selectivity
EX: epi –> isoproternol (add bulky group = beta selective)
isproternol –> metaproternol (get rid of catechol ring = B2 selective)
isoproternol –> atenolol (catechol –> para sub = B1 antagonistic)

Question 2

A. Lipinski

Answer 2

Rule of 5

EX: old antihistamines are very lipophilic and can cross BBB

Question 3

Harrold and Zavod

Answer 3

claim drug and plasma protein binding interactions are clinically relevant, however it may be relevant under rare clinical conditions

• acidic–> albumin
• basic –> alpha 1 acid glycoprotein

Question 4

Langmuir

Answer 4

-1st proposed isoesters (compounds or groups of atoms that have the same number and arrangement of electrons)
EX: N-N triple bond and CO triple bond

Question 5

Grimm/ Grimm’s Hydride Displacement Law

Answer 5

• arranged atoms according to valence e-‘s and found addition of a hydride to an atom gave a pseudo atom (EX: N vs CH)
• -> gave analogous physical properties

Question 6

Erlenmeyer/ Erlenmeyer Isoesters

Answer 6

-noted some groups have differences such as ability to ionize, enhance or decrease water solubility and these differences need to be considered when evaluating esoteric compounds

Question 7

Friedman Biososteres

Answer 7

-retention of biological activity after an isometric replacement
EX: procaine –> procainamide
- high bioavailability and high DOA

Question 8

AV Hill

Answer 8

Occupancy Theory; applied law of mass action to relationship between concentration and target occupancy

Question 9

AJ Clark

Answer 9

assumed response is directly proportional to occupancy

Question 10

Hammett

Answer 10

• the electronic effect of substituents should be similar for different organic reactions
• correlates electronic property of a substituent w/ reactivity of aromatic compounds
• can be applicable to estimate reaction rates of newer drugs

Question 11

Coruin Hansch

Answer 11

“father of quantitative structure activity relationships modeling”